In this project we are characterizing circulating growth hormone species in conditions of abnormal human growth. A two stage homologous radioreceptor assay for human growth hormone has been developed utilizing 1M-9 lymphocytes. It has been validated and will be applied to sera of patients with growth failure, growth with inappropriately low growth hormone by radioimmunoassay and to patients with acromegaly. When significant discrepancies are found growth hormone will be separated from larger serum proteins by gel filtration through Sephadex G-100. The isolated growth hormone will be compared to known growth hormone subspecies in respect to molecular size and isoelectric point (isoelectric focusing). Receptors for growth hormone have been detected in rat adipose cell membranes. This receptor in a cell known to respond to growth hormone provides a test system for correlating receptor binding and biologic effects. Preliminary evidence suggests the presence of a comparable hGH receptor in human fat cell membranes. We will further characterize this receptor. This tissue may be appropriate for studies of GH receptor defect in Laron dwarfism. We have developed a radioreceptor assay for insulin-like growth factor II (IGF-II). Preliminary results indicate that the serum levels of this peptide are not as GH dependent as IGF-I. Possible secretion of this peptide by human tumors associated with hypoglycemia is being studied.